Objectives for NS 2: You should be able to define, describe pathogenesis, list lesions and know how to diagnose the following conditions: Cytotoxic, osmotic and vasogenic brain edema) Thiamine-responsive polioencephalomalacia of ruminants Thiamine deficiency in carnivores Lead poisoning Salt poisoning Toxin-induced vasogenic brain edema

Brain swelling (cerebral edema) Response to injury - Brain edema Brain swelling (cerebral edema) Increased intracranial pressure E. Simko WCVM

Blood perfusion pressure Intracranial pressure Response to injury - Brain edema Brain swelling (edema) Blood perfusion pressure Intracranial pressure Ischemic necrosis E. Simko WCVM

Brain edema Cytotoxic (intracellular) Extra cellular edema Osmotic Response to injury - Brain edema Brain edema Cytotoxic (intracellular) Extra cellular edema Osmotic Vasogenic E. Simko WCVM

Diagnosis: Gross: cerebellar coning (herniation) cerebral herniation Response to injury - Brain edema Diagnosis: Gross: cerebellar coning (herniation) cerebral herniation flattened gyri Microscopically neuronal necrosis edema is not evident in most cases E. Simko WCVM

Polioencephalomalacia (PEM) Thiamine-responsive PEM of ruminants Lead poisoning in ruminants Salt poisoning in pigs & occ. in rumin. Hypoxia

Thiamine-responsive polioencephalomalacia Response to injury - Brain edema Cytotoxic edema (cellular degeneration) Thiamine-responsive polioencephalomalacia in ruminants Etiology Disturbance of thiamine production/absorption concentrate ruminal pH change in flora Bacterial thiaminase [sulfur, sulfates, sulfides] in diet or water E. Simko WCVM

Pathogenesis Cytotoxic edema - Thiamine deficiency Thiamine interferes with glucose metabolism and Krebs cycle in CNS ATP production Na/K transport is impaired Intacellular H2O (hydropic degeneration) Cellular swelling (Cytototoxic edema) Energy exhaustion Intacranial pressure & blood perfusion Ischemic necrosis E. Simko WCVM

Lesions Histology Brain swelling Cytotoxic edema - Thiamine deficiency (flattened gyri, cerebellar coning) Yellow cortical discoloration (autofluorescence under UV light) Cortical liquefaction and cavitation Histology Laminar cortical necrosis E. Simko WCVM

Diagnosis History Response to thiamine Gross and histologic lesions Cytotoxic edema - Thiamine deficiency Diagnosis History Response to thiamine Gross and histologic lesions Rule out the other causes of PEM E. Simko WCVM

Dietary thiamine deficiency in carnivores Cytotoxic edema - Thiamine deficiency Dietary thiamine deficiency in carnivores Dog, cat, mink (Human – Wernicke’s encephalopathy) Depend on exogenous source of vitamin Pathogenesis: diet with thiaminase, sulfur preservatives or exposed to high temperature Lesions: Symmetrical necrosis of thalamic and mid-brain nuclei E. Simko WCVM

Lead poisoning Brain edema Lesions: Source: Old batteries and paint Polioencephalomalacia similar to thiamine resp. Cattle Lead shotgun pellets PNS degeneration (Esophageal/crop dilation and impaction) Waterfowl E. Simko WCVM

Pathogenesis in cattle Brain edema - Lead poisoning Pathogenesis in cattle Direct endothelial injury vasogenic edema Damaged metabolism cellular swelling Energy exhaustion Increased intracranial pressure Failure of blood perfusion Ischemic necrosis E. Simko WCVM

Diagnosis Gross and histologic lesions Lead particles in the rumen Brain edema - Lead poisoning Diagnosis Gross and histologic lesions Lead particles in the rumen Lead level in liver and kidney E. Simko WCVM

Osmosis and semi-permeable cellular membrane Swelling Hypo Os Hypo Os Shrinkage Hyper Os Hyper Os

N N Osmotic brain edema Water intoxication ( IV H2O, behavioral, ADH) Dehydr. Dehydr. BRAIN PLASMA BRAIN PLASMA E. Simko WCVM

N N Water deprivation +/- high salt Osmotic brain edema - Salt toxicity Water deprivation +/- high salt NaCl H2O t = 0 hr Edema Edema N N Cl- Na+ Cl- Na+ Cl- Cl- Na+ Dehydr. Cl- Na+ Dehydr. Cl- Na+ Na+ Na+ Na+ Na+ Na+ Cl- Cl- Cl- Na+ Cl- BRAIN PLASMA NormoNa HyperNa BRAIN PLASMA NormoOs HyperOs Dehydration Dehydration

N N Equilibration of CNS hyperNa Osmotic brain edema - Salt toxicity t = > 36 hr Edema Edema N N AA Cl- Na+ Cl- Cl- Na+ Cl- Na+ Cl- Dehydr. Cl- Cl- Na+ Cl- AA Na+ Cl- Dehydr. Cl- Na+ Na+ Na+ Cl- Na+ Na+ Cl- Na+ Na+ Na+ Cl- BRAIN PLASMA BRAIN PLASMA NormoNa HyperNa HyperNa HyperNa HyperOs HyperOs HyperOs HyperOs Dehydration Dehydration Dehydration Dehydration

N N Water access Osmotic brain edema - Salt toxicity H2O Edema Edema t = > 36 hr H2O Edema Edema N N AA AA Cl- Na+ Na+ Cl- Na+ Cl- Cl- Dehydr. Cl- Dehydr. Na+ AA Na+ AA Cl- Cl- Na+ Na+ Na+ Cl- Na+ Cl- Na+ BRAIN PLASMA BRAIN PLASMA NormoNa HyperNa NormoNa NormoNa HyperOs HyperOs HyperOs NormalOs Dehydration Dehydration Edema Normal hydr.

Lesions Histology Brain swelling Osmotic brain edema - Salt toxicity Cerebrocortical necrosis (occ) Histology Laminar cerebrocortical necrosis Perivascular eosinophilic infiltrate (Po) E. Simko WCVM

Diagnosis History Gross and histologic lesions Na level in the brain Osmotic brain edema - Salt toxicity Diagnosis History Gross and histologic lesions Na level in the brain E. Simko WCVM

Vasogenic brain edema Vasogenic brain edema The most common type of brain edema Pathogenesis: damaged BBB Examples: Toxins Inflammatory processes (H. somnus) E. Simko WCVM

White matter Grey matter E. Simko WCVM

Toxin-induced Toxins Vasogenic brain edema - Salt toxicity Shigella toxin type II (Edema disease) Po Fibrinoid vasculitis Epsilon toxin (C. perfringens D enterotoxemia) Ov Symmetrical encephalomalacia Fumonisin B1 (Fusarium momiliforme) Moldy corn Equine leucoencephalomalacia E. Simko WCVM

Necrosis Trauma Thiamine deficiency Lead poisoning Salt poisoning Response to injury - Necrosis Necrosis Trauma Thiamine deficiency Lead poisoning Salt poisoning Edema disease Clostridial eterotoxemia Equine leucoencephalomalacia Infarction

Infarction